INVESTIGATION OF LIGAND SIZE ON TARGETED PLGA NANOPARTICLES FOR HER2 BREAST CANCER: TRASTUZUMAB AND ITS ScFv ANTI-HER2 ANTIBODY

This research focuses on assessing the effect of various formulation parameters on targeting human epidermal growth factor receptor-2 (HER2) specifically in breast cancer. Poly (D, L-lactide-co-glycolide) (PLGA) polymer, which is approved by FDA, was used to form nanoparticles (NPs) encapsulating docetaxel (DOC) as chemotherapy. HER2 antibody moieties, either whole IgG (TrAb) or single chain fragment variable (ScFv), were decorated on the PLGA NPs surface and evaluated in terms of their ability to target HER2 breast cancer cells. We observed the effects of these NPs against different cell lines (MCF-7 and SK-BR-3). Thus, ligand modified structurally concealed PLGA NPs could be a promising delivery tool for targeting HER2 breast tumor in vitro that improves the release of chemotherapy while reducing the systemic side effects. A solvent evaporation procedure was adjusted to form NP formulations using both ester and carboxylic acid terminated PLGA. Incorporation of ligands (TrAb or ScFv) was conducted through chemical covalent conjugation processes by using different cross-linkers bis(sulfo-succinimidyl) (BS3) or N-hydroxysuccinimide esters (NHS) and 1-ethyl-3-(-3-dimethylaminopropyl) carbodiimide hydrochloride (EDC). The size, zeta potential, polydispersity index, which were determined for the physicochemical characterizations. The physicochemical characterizations of formulations were executed to assess the effects of different ligands in vitro for drug targeting. Also, Fourier Transform Infrared (FTIR) was used to conform the covalent bond insertion between the linkers and ligands (TrAb or ScFv). DOC loading was quantified by a fully validated mass spectrometry method and antibody (Ab) quantification was performed by using the bicinchoninic acid (BCA) assay. Moreover, in vitro drug release profile was assessed. In vitro cellular targeting was examined by measuring the level of HER2 expression through Fluorescence-activated cell sorting (FACS) in two cell lines as well as western blot analysis. Cytotoxicity assay was performed in SK-BR-3 cell line for all the formulations. Modified PLGA NPs showed a mean diameter particle size below 400 nm with approximately neutral zeta potential; for example, ScFv-DOC-Ester PLGA NPs formulation size was 312 8.769 nm, and their zeta potential was 0.024 0.075 mV. The average size of the acidic PLGA TrAb-DOC NPs was 382.5 21.5 nm, and their zeta potential was 0.045 0.037 mV. DOC encapsulation efficiency reached up to 65% to 85% depending on the type of the NPs formulations, and the amount of anti-HER2 attachment efficiency exceeded 40%. The cellular targeting of nanoparticles was studied using two cell lines MCF-7 (low HER2 expression) and SK-BR-3 (high HER2 expression), and different levels of HER2 expression were evaluated. The significant reduction in the level of HER2 expression was observed for all modified NPs formulations in HER2 overexpressed SK-BR-3 cells. Overall, in vitro targeting further demonstrated that modified NPs accumulated DOC in tumor cell line more efficiently than conventional medication. The TrAb conjugated to DOC modified NPs formulations were able to increase the HER2 targeting for DOC compared to ScFv modified NPs. In SK-BR-3 cells, the cytotoxicity of modified NPs was more potent than the conventional DOC due to the targeting, and slow release of DOC from the modified NPs. This system has the potential of improving the targeting and the release of chemotherapeutic drugs into the tumor cells while reducing the side effects caused by affecting healthy tissues. Our data demonstrated that the high affinity for anti-HER2 modified PLGA NPs formulations to efficiently and explicitly target DOC to the HER2 overexpressing cancer cells can be exploited as a potential strategy for chemotherapeutic drug delivery system for HER2 overexpressing breast cancers. Thus, ligand modified structurally concealed PLGA NPs could be a promising delivery tool for targeting HER2 breast tumor in vivo that improves the release of chemotherapy while reducing the systemic side effects

A Study of The Geometrical Optimization and ‎Energies of Carbon Nanoribbons: B3LYP/DFT

يشتمل البحث الحالي على الامثلية الهندسية والطاقات ثلاث تراكيب من شرائط الكاربون النانوية باستخدام الهجينة ذات المعاملات الثلاث من طريقة دالية الكثافة. تم تطبيق الدوال الاساس 6-31G لدراسة تأثير طول الشرائط على الطاقات والخواص الالكترونية للتراكيب. بينت النتائج ان الدالة الهجينة المستعملة كانت مناسبة لحسابات المعاملات الهندسية للتراكيب. كما ان فجوة الطاقة قد ازدادت بزيادة طول الشريط نتيجة لتغير طاقات كل من المستوي الجزيئي العلوي المشغول والمستوي الجزيئي السفلي الفارغ لشرائط الكاربون النانوية. الشريط الاقصر طولاً يمتلك اعلى مرونة الكترونية وفعالية اكبر من الشريط الاطولThis study deals with the geometrical optimization and energies of three structures of carbon nanoribbon using the B3LYP-DFT hybrid functional. 6-31G basis sets was employed to study the effect of the ribbons length on the energies and electronic properties of the structures. The results showed that the hybrid functional used is suitable for calculations the geometrical parameters of the structures. So, the energy gap was increased with increasing the length of the ribbon due to the change  of both the HOMO and LUMO energies of the carbon nanoribbons. The shortest the ribbon the higher electronic softness and the more reactive it is as compared to the long ribbo

Changing Eating Habits in Connection with Environmental Problems in the Eastern Region of Saudi Arabia

The agricultural lands of Saudi Arabia cannot support feeding the population since they have been facing environmental problems including climate change and water scarcity (DeNicola et al. 2015). Food security is the issue, especially in desert countries which rely on natural water resources. Saudi Arabia is one of these desert countries which has been struggling to meet their domestic food demand. Currently Saudi Arabia has been focused on importing most food commodities to meet local food demands in order to mitigate stress on depleting water resources (FAO 2017). Little is understood about how an individual’s food choices can play a significant role in achieving environmental sustainability as well as food security. Therefore, there is a need for more place-based studies that consider the human dimensions of environmental problems. Regarding human dimensions provides a better understanding of the links between dietary choices and environmental consequences. Food choices of individuals can be expected to differ based on the social and cultural context of specific communities. Therefore, the approach of dietary choices and environmental consequences is adopted in this research study which focuses on women who are responsible for feeding their families in the Eastern Region of Saudi Arabia. The main aim is to understand how women choose to feed their families and how changes in consumption, over the years, affect the environment. The study focuses specifically on the frequency of meat consumption and the factors that affect what women choose to feed their families and to explore their perceptions of the connections between food choice and environmental problems. Major themes emerged from this qualitative analysis. Research interviews reflect that women maintain their families’ cultural tradition in consuming meat and dairy products. Meanwhile, lifestyle changes over the years influence dietary habits in shifting towards western foods. The main drivers of food choices, among women, were health, cultural factors and accessibility of restaurants. There was awareness, among the women, about the impacts of dietary choices on their health. However, these women didn’t recognize the impacts of their dietary choices on their environment. This study suggests creating awareness among women to promote environmental sustainability by shifting their diets, which will also promote healthy life styles as well as reducing environmental impacts

Phenolic Compounds in the Built Environment

This chapter examines source and application of phenolic compounds in the built environment as well as their environmental fate and treatment methods. We further describe the role of phenolic compounds in delaying aging and degradation of outdoor construction elements when exposed to intense solar radiation. In this chapter both plant-based and synthetic sources of phenolic compounds and their fate in the environment were examined. In addition, merits of select sources of phenolic compounds to resist ultraviolet radiation in composites as well as delaying degradation were studied. This chapter further provides insights pertaining to the underlying molecular interactions which afford phenol’s role as an anti-aging additive for outdoor construction elements. This in turn provides a solution to promote bio-economy and enhance sustainability in the built environment

Evaluation of LL 37 Lipoprotein as Innate Immunity Marker among Sudanese Patients Cutaneous Leishmania

Background: The leishmaniasis is a group of diseases with a broad range of clinical manifestations caused by several species of parasites belonging to the genus Leishmania. LL-37/hCAP18, the only cathelicidin in human, is expressed as an 18-kDa preproprotein. The most prominent function of cathelicidins is their ability to inhibit propagation of a diverse range of microorganisms, which occurs at a micromolar range. Aim: The study was aimed to evaluate the LL37 plasma level in Leishmania Sudanese patients. Materials and Methods: In a case-control study, three hundred subjects were enrolled (200 as case and 100 controls). Five ml. of venous blood was collected in EDTA container, then plasma was obtained and stored frozen at -80ºC. LL 37 was estimated using competitive ELISA. The data were analyzed using SPSS version 21. Results: The results revealed that 115 (57%) of Leishimania patients were male and 85 (43%) were female. Plasma LL 37 level was significantly increased in Leishmania patients (1.30±0.71) compared to the control (0.21±0.20) with (p-value 0.000). Conclusion: Leishmania patients had higher levels of plasma LL37, suggesting effective anti-microbial immunity process enhancing healing of cutaneous leishmaniasis. Keywords:  Cathelicidins; LL37, Innate Immunity, Leishmania , Sudan

Clinical and genetic assessment of pediatric patients with Gaucher’s disease in Upper Egypt

Background: Gaucher’s disease (GD) is an autosomal recessive genetic disorder that results from pathogenic mutations of GBA gene encoding the enzyme glucocerebrosidase (acid b-glucosidase). Of the approximately 300 mutations associated with GD, 4 accounts for the majority of mutations seen in GD patients: N370S, L444P, 84 GG and IVS2+1.Aim: Establishing and providing, clinical and molecular backgrounds of pediatric patients with GD in Upper Egypt.Subjects and methods: The present study is a cross sectional study, carried out on 26 pediatric patients with GD. They were recruited from the pediatric outpatient clinics and inpatients Pediatric departments of Assiut and Qena University hospitals, Upper Egypt. Clinical evaluation and mutation analysis using commercially available strip assay kit after PCR amplification of the target gene were done for all included GD patients.Results: Consanguinity between patients’ parents was present in 73.1% of the included patients. 76.9% of included patients were of type 1 GD, while 23.1% were of type 3 GD and none of our patients was classified as type 2 GD. The main frequent clinical presentations of GD in this study were hepatosplenomegaly (88.5%); pallor (76.9%); abdominal distension (61.5%) and musculoskeletal involvement (37.1%). Neurological abnormalities of type 3 GD included in this study were squint, seizures and delayed mental development. Five different genotypes were detected, homozygous for the mutation L444P, homozygous for the mutation N370S, heterozygous for the mutations N370S and rec Ncil, heterozygous for IVS2 +1 and rec NciI, heterozygous for L444P and IVS2 +1. Conclusions: Non-neuropathic type 1 and type 3 GD were the only clinical types found in the present study. The most common mutant alleles found in this study were L444P and N370S

Optimizing FPGA-based CNN accelerator for energy efficiency with an extended Rooine model

In recent years, the convolutional neural network (CNN) has found wide acceptance in solving practical computer vision and image recognition problems. Also recently, due to its exibility, faster development time, and energy efficiency, the field-programmable gate array (FPGA) has become an attractive solution to exploit the inherent parallelism in the feedforward process of the CNN. However, to meet the demands for high accuracy of today's practical recognition applications that typically have massive datasets, the sizes of CNNs have to be larger and deeper. Enlargement of the CNN aggravates the problem of off-chip memory bottleneck in the FPGA platform since there is not enough space to save large datasets on-chip. In this work, we propose a memory system architecture that best matches the off-chip memory traffic with the optimum throughput of the computation engine, while it operates at the maximum allowable frequency. With the help of an extended version of the Rooine model proposed in this work, we can estimate memory bandwidth utilization of the system at different operating frequencies since the proposed model considers operating frequency in addition to bandwidth utilization and throughput. In order to find the optimal solution that has the best energy efficiency, we make a trade-off between energy efficiency and computational throughput. This solution saves 18% of energy utilization with the trade-off having less than 2% reduction in throughput performance. We also propose to use a race-to-halt strategy to further improve the energy efficiency of the designed CNN accelerator. Experimental results show that our CNN accelerator can achieve a peak performance of 52.11 GFLOPS and energy efficiency of 10.02 GFLOPS/W on a ZYNQ ZC706 FPGA board running at 250 MHz, which outperforms most previous approaches

The influence of size and shape of Neodymium-doped:Yttrium Aluminium Garnet (Nd:YAG) laser capsulotomy on visual acuity and refraction

Background: Posterior capsule opacification is the most common complication of cataract surgery and results from the proliferation and migration of residual lenticular epithelial cells. Opacification may be diminished by atraumatic surgery; complete cleaning of cortex residues, polishing of both anterior and posterior capsules, clinical, pathological and experimental studies have shown that use of hydrodissection, the continuous curvilinear capsulorhexis or the use of specific intraocular lens (IOL) designs. The overall incidence of posterior capsule opacification (PCO) approaches 50% at 5 years following cataract surgery and disproportionately affects younger patients due to higher cell proliferation rates. Capsular-fixated, one-piece all-polymethylmethacrylate PC-IOLs with a Cshaped loop configuration and a posterior convexity of the optic are effective in reducing PCO. Objectives:To evaluate the influence of size and shape of neodymium: yttrium aluminum- Garnet (Nd:YAG) laser capsulotomy on visual acuity and refraction. Patients and method(s): A prospective study was performed in department of ophthalmology at Qena university hospital between September 2016 and September 2017. Informed consent was obtained from each patient before the study. A South Valley University institutional ethics committee approval was obtained. In this study 60 pseudophakic eyes of 58 patients of age range (30-70years) were included. All of the patients had undergone non complicated cataract surgery (phacoemulsification (48eyes) or extracapsular cataract extraction (12 eyes)). Result(s): All patients had significant vision loss and hazy fundus appearance due to posterior capsular opacification. There was significant improvement in VA in the four groups, with statistically significant improvement effect of cruciate shape capsulotomy with size >3.5mm on BCVA. Conclusion:The cruciate 0shape with size more than 3.5 mm capsulotomy openings show better improvement in BCVA than the other groups. Spherical equivalent show slight improvement in all groups which was insignificant

Staged hepatectomy for bilobar colorectal hepatic metastases

AbstractObjectivesThis study describes the management of patients with bilobar colorectal liver metastases (CRLM).MethodsA retrospective collection of data on all patients with CRLM who were considered for staged resection (n= 85) from January 2003 to January 2011 was performed. Patients who underwent one hepatic resection were considered to have had a failed staged resection (FSR), whereas those who underwent a second or third hepatic resection to produce a cure were considered to have had a successful staged resection (SSR). Survival was calculated from the date of diagnosis of liver metastases. Complete follow-up and dates of death were obtained from the Government of Quebec population database.ResultsMedian survival was 46months (range: 30–62months) in the SSR group and 22months (range: 19–29months) in the FSR group. Rates of 5-year survival were 42% and 4% in the SSR and FSR groups, respectively. Fifteen of the 19 patients who remained alive at the last follow-up date belonged to the SSR group.ConclusionsIn patients in whom staged resection for bilobar CRLM is feasible, surgery would appear to offer benefit